Strain Name:

B6.Cg-Mapkapk2tm1.1Yaff/J

Stock Number:

024176

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Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use
The MK2CV allele has exon 2 of the MAP kinase-activated protein kinase 2 gene flanked with loxP sites in opposing orientations. A single exposure to Cre recombinase inverts exon 2; this generates a STOP codon and results in a functional null allele. In addition, exon 2 can switch reversibly between the MK2-expressing and MK2-null orientation as long as Cre recombinase is active in the cell. These MK2CV mice may be useful in studying the p38 MAP kinase/MK2 pathway, other checkpoint control pathways, DNA damage response, DNA repair, cell cycle arrest and apoptosis; as well as with other cancer models to study sensitization of tumors to DNA-damaging chemotherapeutics in vivo.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Michael B Yaffe,   Massachusetts Institute of Technology

Description
The MK2CV allele has exon 2 of the MAP kinase-activated protein kinase 2 gene flanked with inward-facing loxP sites (loxP sites in opposing orientations). Homozygous mice are viable and fertile. Prior to Cre recombinase exposure, exon 2 is in the wildtype configuration (MK2+CV); resulting in normal MK2-expression. A single exposure to Cre recombinase creates the inverted exon 2 configuration (MK2-CV); the resulting transcript has a STOP codon in the beginning of exon 3 that encodes a highly truncated reading frame that is not translated into functional MK2 proteins (i.e., loss of both the 46 KDa and 42 KDa isoforms corresponding to Uniprot P49137-1 and P49137-2 for human MK2). Because inward-facing loxP sequences result in cre-mediated inversion rather than excision, exon 2 can reversibly switch from the MK2-expressing orientation (MK2+CV) to the MK2-null orientation (MK2-CV) and back as long as Cre recombinase is active in the cell. In addition, the MK2 expression state that is established by a single Cre recombinase pulse (e.g., germline cre expression or transient cre expression via adenoviral injection) within the cell is maintained throughout further daughter cell generations.

These MK2CV mice may be useful in studying the p38 MAP kinase/MK2 pathway, other checkpoint control pathways, DNA damage response, DNA repair, cell cycle arrest and apoptosis; as well as with other cancer models to study sensitization of tumors to DNA-damaging chemotherapeutics in vivo.

For example, when MK2CV mice are bred to harbor the KrasLSL-G12D and p53flox alleles (see Stock Nos. 008179 and 008462, respectively), administration of a Cre recombinase-expressing adenovirus generates mosaic MK2-deficient or MK2-proficient non-small cell lung adenocarcinomas in the same animal. This allows one to study the role of MK2 in cancer development, progression, and response to DNA-damaging chemotherapy in non-small cell lung cancer.

Development
A targeting vector created by Dr. Michael B. Yaffe (Massachusetts Institute of Technology) was designed to insert a loxP site upstream of exon 2, and a second loxP site (in reverse complement sequence to the first loxP site) downstream of exon 2 of the MAP kinase-activated protein kinase 2 gene (Mapkapk2). This also placed a frt:PGK-neo:frt sequence downstream of the second loxP site. This construct was electroporated into (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells. Chimeric males were bred with ACTB-FLPe transgenic mice (backcrossed eight generations onto C57BL/6J) to eliminate the frt-flanked PGK-neo cassette. The resulting mice with inward-facing loxP sites flanking exon 2 (and a single frt site remaining downstream of exon 2) were identified and termed MK2 "Cre-versible" mice (or MK2CV mice). The MK2CV colony was then backcrossed to C57BL/6J inbred mice for ten generations (and the FLPe transgene was removed) prior to sending to The Jackson Laboratory Repository in 2014. Upon arrival, sperm was cryopreserved. To generate the living MK2CV colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J female mice (Stock No. 000664). The MK2CV colony was then maintained by breeding heterozygous mice with wildtype mice from the colony or with C57BL/6J inbred mice.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mapkapk2
005850   B6.129P2-Mapkapk2tm1Dgen/J
View Strains carrying other alleles of Mapkapk2     (1 strain)

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Mapkapk2tm1.1Yaff/Mapkapk2tm1.1Yaff

        involves: 129S4/SvJae * C57BL/6
  • normal phenotype
  • no abnormal phenotype detected
    • homozygotes are viable and fertile   (MGI Ref ID J:203686)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Apoptosis Research
Endogenous Regulators
Extracellular Modulators

Cancer Research
Cre-lox System
      loxP-flanked Sequences
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines
Oncogenes
Other
      DNA Repair
Tumor Resistance
Tumor Suppressor Genes

Cell Biology Research
Cell Cycle Regulation
DNA Damage Response
Genes Regulating Growth and Proliferation
Signal Transduction
Transcriptional Regulation

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules

Neurobiology Research
Cre-lox System
      loxP-flanked Sequences

Research Tools
Apoptosis Research
Cancer Research
      Cre-lox System
      anti-tumor activity
Cardiovascular Research
      Cre-lox System
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Genetics Research
      Mutagenesis and Transgenesis: Cre-lox System
      Mutagenesis and Transgenesis: transcriptional activation
      Tissue/Cell Markers: Cre-lox System
Reproductive Biology Research
      Cre-lox System

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mapkapk2tm1.1Yaff
Allele Name targeted mutation 1.1, Michael Yaffe
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) MK2CV;
Strain of Origin(C57BL/6 x 129S4/SvJae)F1
Gene Symbol and Name Mapkapk2, MAP kinase-activated protein kinase 2
Chromosome 1
Gene Common Name(s) AA960234; MAPKAP kinase 2; MAPKAP-K2; MK-2; MK2; Rps6kc1; expressed sequence AA960234; ribosomal protein S6 kinase, 60 kDa, polypeptide 1;
Molecular Note A targeting vector was designed to insert a loxP site upstream of exon 2, and a second loxP site (in reverse complement sequence to the first loxP site) downstream of exon 2 as well as a frt:PGK-neo:frt sequence downstream of the second loxP site. Because inward-facing loxP sequences result in cre-mediated inversion rather than excision, exon 2 can reversibly switch from Mapkap2 expression orientation (MK2<+CV>, CV; Cre-versible) to the null orientation (MK2<-CV>) and back as long as Cre recombinase is active in the cell.FLP recombinase mediated recombination removed the neomycin cassette. [MGI Ref ID J:203686]

Genotyping

Genotyping Information

Genotyping Protocols

Mapkapk2tm1.1Yaff, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Morandell S; Reinhardt HC; Cannell IG; Kim JS; Ruf DM; Mitra T; Couvillon AD; Jacks T; Yaffe MB. 2013. A Reversible Gene-Targeting Strategy Identifies Synthetic Lethal Interactions between MK2 and p53 in the DNA Damage Response In Vivo. Cell Rep 5(4):868-77. [PubMed: 24239348]  [MGI Ref ID J:203686]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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